Human Microdosing/Phase 0 Studies to Accelerate Drug Development

Microdosing Phase 0 studies provide early information about a drug's pharmacokinetics and limited pharmacodynamics before expensive Phase I trials. Developed in the 2000s, this method helps select drug candidates and uses ultrasensitive accelerator mass spectrometry. The chapter reviews the scientific, regulatory, ethical, and commercial aspects of microdosing, arguing that because the best model for humans is human, microdose studies should replace early in vitro and preclinical work as more relevant and predictive of a drug's ADME at therapeutic doses, offering a new paradigm for early drug development.

Study at a glance

Abstract

Human microdosing Phase 0 studies are used to obtain key information in early drug development concerning a drug's pharmacokinetic and limited pharmacodynamic parameters. Developed as a method in the 2000s, microdosing has become part of the critical path of drug development. Microdosing studies can assist in drug candidate selection prior to going into expensive Phase I studies. This chapter provides a historical perspective of microdose studies, details the steps involved in conducting a successful microdose study and highlights the value of the ultrasensitive bioanalytical technology accelerator mass spectrometry in microdose study conduct. The scientific, regulatory, ethical and commercial aspects of microdosing are reviewed, together with where the method has most utility. On the basis that the best model for humans is human, the chapter explains why microdose studies should be undertaken at the expense of early in vitro and preclinical studies as being more relevant and predictive of a drug's ADME at therapeutic doses and thus provide a new paradigm for early drug development.